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1. 发明授权

US07667089B2 Transgenic mammal secreting B-domain deleted human FVII in its milk 有权
标题翻译：转基因哺乳动物在其牛奶中分泌B结构域缺失的人FVII
公开(公告)号：US07667089B2
公开(公告)日：2010-02-23
申请号：US10820777
申请日：2004-04-09
申请人： Winston T. K. Cheng , Chuan-Mu Chen , Shwu-Wha Lin , Chih-Hong Wang , Chih-Jen Lin , Shinn-Chih Wu
发明人： Winston T. K. Cheng , Chuan-Mu Chen , Shwu-Wha Lin , Chih-Hong Wang , Chih-Jen Lin , Shinn-Chih Wu
IPC分类号： C12P21/00 , A01K67/027 , C12N15/00
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2267/01 , C07K14/755 , C12N2830/008
摘要： Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland. These gene cassettes are capable of delivering different transgenic constructs which result in the production of full-length or B domain-deleted therapeutic levels of biologically active human FVIII in the transgenic animals in vivo. Within the scope of the invention are also method for producing the transgenic non-human mammal, such as mouse, rat, rabbit, goat, sheep, pig and bovine species, capable of expressing human FVIII, and methods of making milk and methods of identifying protein from the transgenic milk.
摘要翻译：血友病A是凝血因子VIII（FVIII）缺乏或异常引起的主要遗传性出血性疾病之一。已经用全血浆或纯化的FVIII浓缩物治疗血友病患者。传播血源性病毒的风险和高度纯化的FVIII的成本是限制血友病治疗预防的主要因素。生物技术革命带来的挑战之一是开发大规模经济生产高纯度蛋白质的方法。本发明提供了可用于在转基因动物的牛奶中高水平表达基因的改进的乳腺表达盒。特别地，本发明提供了衍生自α-乳白蛋白的重组信号肽序列和适合于在乳腺中引导蛋白质分泌的α1酪蛋白乳基因。这些基因盒能够递送不同的转基因构建体，其导致在转基因动物体内产生全长或B结构域缺失的生物活性人类FVIII的治疗水平。在本发明的范围内，也是用于生产能够表达人FVIII的转基因非人哺乳动物如小鼠，大鼠，兔，山羊，绵羊，猪和牛物种的方法，以及制备牛奶的方法和鉴定方法来自转基因乳的蛋白质。

2. 发明申请

US20050229261A1 Method for producing biologically active human factor VIII in the milk of transgenic animals driven by mammary-specific expression cassettes 有权
标题翻译：在乳腺特异性表达盒驱动的转基因动物的乳中生产生物活性人因子VIII的方法
公开(公告)号：US20050229261A1
公开(公告)日：2005-10-13
申请号：US10820777
申请日：2004-04-09
申请人： Winston Cheng , Chuan-Mu Chen , Shwu-Wha Lin , Chih-Hong Wang , Chih-Jen Lin , Shinn-Chih Wu
发明人： Winston Cheng , Chuan-Mu Chen , Shwu-Wha Lin , Chih-Hong Wang , Chih-Jen Lin , Shinn-Chih Wu
IPC分类号： A01K67/027 , C07K14/755 , C12N15/85
CPC分类号： C12N15/8509 , A01K67/0275 , A01K2217/05 , A01K2267/01 , C07K14/755 , C12N2830/008
摘要： Hemophilia A is one of the major inherited bleeding disorders caused by a deficiency or abnormality in coagulation factor VIII (FVIII). Hemophiliacs have been treated with whole plasma or purified FVIII concentrates. The risk of transmitting blood-borne viruses and the cost of highly purified FVIII are the major factors that restrict prophylaxis in hemophilia therapy. One of the challenges created by the biotechnology revolution is the development of methods for the economical production of highly purified proteins in large scales. The present invention provides improved mammary expression cassettes useful for the expression of genes at high levels in the milk of transgenic animals. In particular, the present invention provides recombinant signal peptide sequences derived from a-lactalbumin and aS1-casein milk genes suitable for leading protein secretion in the mammary gland. These gene cassettes are capable of delivering different transgenic constructs which result in the production of full-length or B domain-deleted therapeutic levels of biologically active human FVIII in the transgenic animals in vivo. Within the scope of the invention are also method for producing the transgenic non-human mammal, such as mouse, rat, rabbit, goat, sheep, pig and bovine species, capable of expressing human FVIII, and methods of making milk and methods of identifying protein from the transgenic milk.
摘要翻译：血友病A是凝血因子VIII（FVIII）缺乏或异常引起的主要遗传性出血性疾病之一。已经用全血浆或纯化的FVIII浓缩物治疗血友病患者。传播血源性病毒的风险和高度纯化的FVIII的成本是限制血友病治疗预防的主要因素。生物技术革命带来的挑战之一是开发大规模经济生产高纯度蛋白质的方法。本发明提供了可用于在转基因动物的牛奶中高水平表达基因的改进的乳腺表达盒。特别地，本发明提供了衍生自α-乳白蛋白的重组信号肽序列和适合于在乳腺中引导蛋白质分泌的α1酪蛋白乳基因。这些基因盒能够递送不同的转基因构建体，其导致在转基因动物体内产生全长或B结构域缺失的生物活性人类FVIII的治疗水平。在本发明的范围内，也是用于生产能够表达人FVIII的转基因非人哺乳动物如小鼠，大鼠，兔，山羊，绵羊，猪和牛物种的方法，以及制备牛奶的方法和鉴定方法来自转基因乳的蛋白质。

3. 发明授权

US07795234B2 Newly identified human small intestine extracellular lactase-phlorizin hydrolase (ecLPH) gene 有权
标题翻译：新鉴定的人类小肠细胞外乳糖酶 - 根皮苷水解酶（ecLPH）基因
公开(公告)号：US07795234B2
公开(公告)日：2010-09-14
申请号：US11901989
申请日：2007-09-20
申请人： Chuan-Mu Chen , Winston T. K. Cheng , Hsiao-Ling Chen
发明人： Chuan-Mu Chen , Winston T. K. Cheng , Hsiao-Ling Chen
IPC分类号： A01N43/04 , C07H21/04 , C12N15/00
CPC分类号： C12N9/2405 , A01K67/0275 , A01K2217/05 , A01K2227/101 , A01K2227/102 , A01K2227/103 , A01K2227/105 , A01K2267/02 , C07K2319/02 , C12N15/8509 , C12N2830/008 , C12Y302/01108
摘要： The invention provides a transgenic animal producing low-lactose milk, which is transformed with a gene encoding an extracellular lactase-hydrolyzing enzyme cloned from a human small intestinal cDNA library. The invention also provides a new extracellular lactase-phlorizin hydrolase (ecLPH) gene that can express human lactase-hydrolyzing enzyme in the mammary gland of animals. The invention can be used in the production of low-lactose milk.
摘要翻译：本发明提供一种产生低乳糖的转基因动物，其用编码从人小肠cDNA文库克隆的细胞外乳糖酶水解酶的基因转化。本发明还提供了可以在动物乳腺中表达人乳糖酶水解酶的新的细胞外乳糖酶 - 根皮苷水解酶（ecLPH）基因。本发明可用于生产低乳糖乳。

4. 发明授权

US07501554B2 Transgenic animals producing low-lactose milk and newly identified human small intestinal extracellular lactase-phlorizin hydrolase (ecLPH) gene 有权
标题翻译：产生低乳糖乳和新鉴定的人小肠细胞外乳糖酶 - 根皮苷水解酶（ecLPH）基因的转基因动物
公开(公告)号：US07501554B2
公开(公告)日：2009-03-10
申请号：US11434332
申请日：2006-05-15
申请人： Chuan-Mu Chen , Winston T. K. Cheng , Hsiao-Ling Chen
发明人： Chuan-Mu Chen , Winston T. K. Cheng , Hsiao-Ling Chen
IPC分类号： A01K67/027 , C12N15/00
CPC分类号： C12N9/2405 , A01K67/0275 , A01K2217/05 , A01K2227/101 , A01K2227/102 , A01K2227/103 , A01K2227/105 , A01K2267/02 , C07K2319/02 , C12N15/8509 , C12N2830/008 , C12Y302/01108
摘要： The invention provides a transgenic animal producing low-lactose milk, which is transformed with a gene encoding an extracellular lactase-hydrolyzing enzyme cloned from a human small intestinal cDNA library. The invention also provides a new extracellular lactase-phlorizin hydrolase (ecLPH) gene that can express human lactase-hydrolyzing enzyme in the mammary gland of animals. The invention can be used in the production of low-lactose milk.
摘要翻译：本发明提供一种产生低乳糖的转基因动物，其用编码从人小肠cDNA文库克隆的细胞外乳糖酶水解酶的基因转化。本发明还提供了可以在动物乳腺中表达人乳糖酶水解酶的新的细胞外乳糖酶 - 根皮苷水解酶（ecLPH）基因。本发明可用于生产低乳糖乳。

5. 发明申请

US20050114911A1 Method for expressing multiple recombinant proteins in milk of transgenic non-human mammals 有权
标题翻译：用于在转基因非人哺乳动物的乳中表达多种重组蛋白的方法
公开(公告)号：US20050114911A1
公开(公告)日：2005-05-26
申请号：US10790720
申请日：2004-03-03
申请人： Shinn-Chih Wu , Teng-Kuei Cheng , Chuan-Mu Chen , Shau-Ping Lin , Chon-Ho Yen , Ping-Cheng Yang
发明人： Shinn-Chih Wu , Teng-Kuei Cheng , Chuan-Mu Chen , Shau-Ping Lin , Chon-Ho Yen , Ping-Cheng Yang
IPC分类号： A01K67/027
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/108 , A01K2267/01
摘要： The present invention discloses a method for expressing multiple recombinant proteins in transgenic non-human mammalian milk, characterized in which human clotting factor IX gene and porcine lactoferrin gene are transferred into the mammal by gene injection and embryonic implantation to obtain expression in the milk of transgenic mammal and its filial generation. The method of this invention can maintain the stable expression of multiple recombinant proteins in the transgenic mammal during lactation and stable expression amount proximate to that of the first generation in the offsprings of the transgenic non-human mammal.
摘要翻译：本发明公开了一种在转基因非人哺乳动物乳中表达多种重组蛋白的方法，其特征在于通过基因注射和胚胎移植将人凝血因子IX基因和猪乳铁蛋白基因转移到哺乳动物中，以获得转基因乳中的表达哺乳动物及其子代。本发明的方法可以在哺乳期间保持转基因哺乳动物中多种重组蛋白的稳定表达，并且在转基因非人哺乳动物的后代中可以保持接近于第一代的稳定表达量。

6. 发明申请

US20100125918A1 ENTEROVIRUS TYPE 71 PROTEIN AND METHOD FOR PRODUCTION 有权
标题翻译： EnterOVIRUS型71蛋白质和生产方法
公开(公告)号：US20100125918A1
公开(公告)日：2010-05-20
申请号：US12274194
申请日：2008-11-19
申请人： Chuan-Mu Chen , Hsiao-Ling Chen
发明人： Chuan-Mu Chen , Hsiao-Ling Chen
IPC分类号： A01K67/027 , C12P21/00 , C07K14/00 , C12N15/11 , C12N15/00 , A61K38/16
CPC分类号： C07K14/005 , A01K67/0275 , A01K2217/052 , A01K2217/206 , A01K2227/105 , A01K2267/01 , A01K2267/0337 , A61K38/00 , A61K39/00 , A61K2039/542 , C07K2319/02 , C12N15/8509 , C12N2770/32322
摘要： The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.
摘要翻译：本发明提供了一种新型的人肠毒素71的衣壳蛋白VP1，命名为MEL701-VP1及其功能/结构变体，其用于保护免于肠道病毒。还提供了产生蛋白质的转基因动物，包含蛋白质的组合物及其生产方法。

7. 发明授权

US08313750B2 Enterovirus type 71 protein and method for production 有权
公开(公告)号：US08313750B2
公开(公告)日：2012-11-20
申请号：US13034355
申请日：2011-02-24
申请人： Chuan-Mu Chen , Hsiao-Ling Chen
发明人： Chuan-Mu Chen , Hsiao-Ling Chen
IPC分类号： A61K39/12 , C07H21/02 , C07H21/04
CPC分类号： C07K14/005 , A01K67/0275 , A01K2217/052 , A01K2217/206 , A01K2227/105 , A01K2267/01 , A01K2267/0337 , A61K38/00 , A61K39/00 , A61K2039/542 , C07K2319/02 , C12N15/8509 , C12N2770/32322
摘要： The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.

8. 发明授权

US08168192B2 Enterovirus type 71 protein and method for production 有权
标题翻译：肠病毒71型蛋白及其生产方法
公开(公告)号：US08168192B2
公开(公告)日：2012-05-01
申请号：US12274194
申请日：2008-11-19
申请人： Chuan-Mu Chen , Hsiao-Ling Chen
发明人： Chuan-Mu Chen , Hsiao-Ling Chen
IPC分类号： A61K39/12 , A61K39/00 , A61K39/38
CPC分类号： C07K14/005 , A01K67/0275 , A01K2217/052 , A01K2217/206 , A01K2227/105 , A01K2267/01 , A01K2267/0337 , A61K38/00 , A61K39/00 , A61K2039/542 , C07K2319/02 , C12N15/8509 , C12N2770/32322
摘要： The invention provides a new type of a capsid protein VP1 of human enterovirus 71, named as MEL701-VP1 and functional/structural variants thereof, which is used for protection against enterovirus. The transgenic animal producing the protein, the composition comprising the protein and the method for production thereof are also provided.
摘要翻译：本发明提供了一种新型的人肠毒素71的衣壳蛋白VP1，命名为MEL701-VP1及其功能/结构变体，其用于保护免于肠道病毒。还提供了产生蛋白质的转基因动物，包含蛋白质的组合物及其生产方法。

9. 发明授权

US08247644B2 Method for manufacturing animal model for researching pulmonary tumor and use thereof 有权
标题翻译：制造肺肿瘤研究动物模型的方法及其应用
公开(公告)号：US08247644B2
公开(公告)日：2012-08-21
申请号：US12828786
申请日：2010-07-01
申请人： Chuan-Mu Chen
发明人： Chuan-Mu Chen
IPC分类号： A01K67/033 , A01K67/00 , C12N15/00
CPC分类号： A01K67/0275 , A01K2217/052 , A01K2227/105 , A01K2267/03 , A01K2267/0325
摘要： The present invention is a method for manufacturing an animal model for researching a pulmonary tumor and a use thereof. A transgenic non-human animal of the present invention is prepared by embryonic gene microinjection and possesses a tissue-specific expression of vascular endothelial growth factor A165 (VEGF-A165) in lung. Through the expression of vascular endothelial growth factor A165, the lung cells in the transgenic non-human animal of the present invention have inflammatory, vascularogenesis and angiogenesis responses or induce lung tumors. Thus, the non-human animal of the present invention can serve as an animal model for analyzing the regulation and the anti-tumor drugs screening of pulmonary adenocarcinoma.
摘要翻译：本发明是一种用于制造用于研究肺肿瘤的动物模型及其用途的方法。通过胚胎基因显微注射制备本发明的转基因非人动物，并且在肺中具有血管内皮生长因子A165（VEGF-A165）的组织特异性表达。通过血管内皮生长因子A165的表达，本发明的转基因非人动物中的肺细胞具有炎性，血管发生和血管生成反应或诱导肺肿瘤。因此，本发明的非人动物可以作为用于分析肺腺癌的调节和抗肿瘤药物筛选的动物模型。

10. 发明授权

US07763281B2 Antihypertensive peptide and use thereof 有权
标题翻译：抗高血压肽及其用途
公开(公告)号：US07763281B2
公开(公告)日：2010-07-27
申请号：US11856262
申请日：2007-09-17
申请人： Hsiao-Ling Chen , Chuan-Mu Chen
发明人： Hsiao-Ling Chen , Chuan-Mu Chen
IPC分类号： A61K35/20 , A61K38/00 , A01N37/18 , C07K5/00
CPC分类号： C07K14/4732 , A23C9/127 , A23L33/18 , A61K38/00
摘要： The present invention provides a novel antihypertensive peptide. Also provided are pharmaceutical and food compositions containing the antihypertensive peptide for treating hypertension or cardiovascular disease.
摘要翻译：本发明提供了一种新的抗高血压肽。还提供含有用于治疗高血压或心血管疾病的抗高血压肽的药物和食品组合物。

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